So you’ve got a teenage child who’s depressed. What do you do? A new study published in the Journal JAMA Internal Medicine suggests what NOT to do. In this study, conducted at Harvard, the authors looked at 162,625 people from ages of 10 to 64 years old who took selective serotonin reuptake inhibitors (SSRIs) for depression. (These are drugs like Paxil, Prozac, Celexa, Zoloft, Lexapro, and Luvox, and their generic equivalents.)
The researchers looked at the relationship between initial starting dose and the rate of deliberate self harm and suicidal behavior. What they found was shocking. They found that for people under the age of 25 starting SSRI medication at a higher than normal dose more than doubled the risk of self harm behavior! This translated into one additional occurrence of self harm behavior for every 136 patients who were treated with high-dose SSRIs. This is a lot of additional suicide attempts!
Interestingly enough, for adults 25 to 64 years old, there was only a very small increase in self harm behavior with high-dose SSRI treatment, and the overall risk of self harm behavior was much lower.
Delving more deeply into the data is interesting. In the under 25-year-old range, 142 patients attempted suicide within one year. The rate was 14.7 suicide events per 1000 person-years for those who started SSRIs at average doses, and 31.5 suicide events per 1000 person-years in those who started at high doses. For the older adults the rates were 2.8 per 1000 person-years for average doses, and 3.2 suicide events per 1000 person-years for those who started at high doses. These numbers translated into seven more suicide events per 1000 for patients under 25 during the first 90 days of treatment with high dose SSRIs.
Also, disturbingly, the study found that 18% of all patients were started on high initial doses of antidepressants, despite clinical guidelines that specifically recommend starting at a low dose and titrating the dose upwards slowly. The typical doses of common antidepressants are 20 mg for Prozac, 20 mg for Paxil, 20 mg for Celexa, 50 mg for Zoloft, and 10 mg for Lexapro. For unknown reasons, almost one in five patients were started at higher doses than these.
Why were almost one in five patients started at higher doses than these? I suspect I know the answer, although it wasn’t discussed in the study. Unfortunately, the vast majority of patients are given antidepressants by their internist or family physician or pediatrician. In contrast to psychiatrists, these practitioners do not have the time or bandwidth see patients every week. So they are more likely to start the patient at a higher dose.
Most psychiatrists will start patients at subclinical doses and gradually increase the dosage to avoid side effects. It certainly has been my clinical experience that some general medicine doctors do not do a very good job of administering antidepressants. That is why with most of my patients, especially if they can afford it or have good insurance coverage, I suggest that they seek the advice of a psychopharmacologist or psychiatrist for psychoactive drugs.
The authors of this paper point out that recent research suggests that antidepressant medication is at best only slightly effective in young people and that the dosage of antidepressants are typically unrelated to their effectiveness. Given these two research findings, it certainly does not make any sense to start antidepressant treatment at a higher than average dose.
But I would go one step further. I would argue more strongly that in most cases it does not make sense to use antidepressant medications in young people at all. Why expose a young person to the heightened risk of suicide for what is at best a relatively modest improvement in mood?
This is even more relevant when you consider that there is an alternative treatment that has no side effects and has been shown to be effective. That is cognitive behavioral therapy (CBT) for depression. And there is even a specific cognitive behavioral therapy for suicide prevention that has been developed. (CBT-SP). This is a 12 week focused CBT program that in one study demonstrated that it significantly lowered the probability of a suicide event in suicidal adolescents.
If medication is going to be used, one recommendation that follows from all of this research is that it is good idea for doctors to follow the guideline of “start low and slow” when prescribing antidepressant medications to people under 25. Start at lower than typical doses, and very slowly and gradually increase the doses. While this is happening the patient should be followed on a weekly basis.
If the prescribing doctor is not a psychiatrist who sees the young person weekly, it’s a good idea to pair this with weekly psychotherapy sessions. The weekly psychotherapy session, especially when conducted by someone skilled in cognitive behavioral therapy who evaluates mood and suicidal ideation at every session, can be an essential safety measure when prescribing antidepressants to young people. Or consider treating with CBT alone, which may very well be just as effective.
Because this is so important, I am listing some references below.
No jokes today, as suicide is not a laughing matter…